E6 and E7 oncoproteins from human papillomavirus type 16 induce activation of human transforming growth factor beta1 promoter throughout Sp1 recognition sequence

Viral Immunol. Summer 2006;19(3):468-80. doi: 10.1089/vim.2006.19.468.

Abstract

Human Papillomavirus (HPV) infection is the main etiologic agent of cervical cancer and HPV E6 and E7 oncogenes trans-regulate many cellular genes. An association between TGF-beta1 gene expression and cervical cancer development has been suggested; however, the mechanisms by which HPV influences TGF-beta1 expression remain unclear. In the present study we analyzed the mechanism through which HPV-16 E6 and E7 oncoproteins regulate the TGF-beta1 promoter in cervical tumor cells. Our results showed that E6 and E7 increased TGF-beta1 promoter activity. Furthermore, we identified a specific DNA sequence motif in the TGF-beta1 core promoter that is responsible for trans-activation and that corresponds to the Sp1e-binding site associated with HPV-16 E6 and E7 oncoproteins. Mutational analysis showed that the Sp1e recognition site abolished the trans-activation caused by E6 and E7. These results suggest a physical interaction and functional cooperation between viral oncoproteins and cellular regulatory elements of the TGF-beta1 promoter, and may explain the contribution of HPV-16 to TGF-beta1 gene expression in cervical cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Extracellular Matrix Proteins / chemistry*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Human papillomavirus 16 / metabolism
  • Human papillomavirus 16 / pathogenicity*
  • Humans
  • Molecular Sequence Data
  • Oncogene Proteins, Viral / metabolism*
  • Papillomavirus E7 Proteins
  • Promoter Regions, Genetic
  • Repressor Proteins / metabolism*
  • Sp1 Transcription Factor / metabolism*
  • Transcriptional Activation*
  • Transforming Growth Factor beta / chemistry*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*

Substances

  • E6 protein, Human papillomavirus type 16
  • Extracellular Matrix Proteins
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Repressor Proteins
  • Sp1 Transcription Factor
  • Transforming Growth Factor beta
  • oncogene protein E7, Human papillomavirus type 16
  • betaIG-H3 protein